Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat

Zouboulis-Vafiadis, Irene; Dumont, M; Erlinger, S

doi:10.1152/ajpgi.1982.243.3.g208

Cited by 19 publications

(20 citation statements)

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“…The excretion of ursodeoxycholate and its glycine conjugate, on the other hand, increased with time, but only slightly, and was not enough to compensate for the decrease in the tauroursodeoxycholate excretion rate. These observations are also agreeable with our previous report (KITANI and KANAI, 1982), but at variance with the much higher proportion of glycoursodeoxycholate in the bile reported by DUMONT et al (1980) and more recently by ZoUBoULIs-VAFIADIS et al (1982). It has been clearly shown in our study that the relative as well as absolute excretion rates of these bile salts are a function of infusion time, while the data presented by the above workers were described only in relation to the infusion rate of the bile salt (DUMONT et al, 1980;ZoUBoULIs-VAFIADIS, 1982).…”

Section: Discussionsupporting

confidence: 94%

“…This agrees with several previous reports including our own (DUMONT et al, 1980;KITANI and KANAI, 1982;ZOUBOULIS-VAFIADIS et al, 1982). In j3-alanine pretreated rats that had the highest bile flow among the three rat groups, the bicarbonate concentration in the bile also increased to the highest level, while in taurine-supplemented rats, the rise in bicarbonate concentration was lowest.…”

Section: Discussionsupporting

confidence: 93%

“…A subsequent report from the same laboratory did not document this phenomenon either (ZoUBoULIs-VAFIADIS et al, 1982). In their recent study, the above workers reported that the maximal biliary excretion rate was much lower with infusion of ursodeoxycholate than with infusion of tauroursodeoxycholate (ZoUBoULIs-VAFIADIS et al, 1982). Their observations are essentially in agreement with our own previous observations KANAI, 1981, 1982).…”

Section: Discussionsupporting

confidence: 70%

“…a further increase in bile flow with a sharp drop in the bile salt excretion rate). A subsequent report from the same laboratory did not document this phenomenon either (ZoUBoULIs-VAFIADIS et al, 1982). In their recent study, the above workers reported that the maximal biliary excretion rate was much lower with infusion of ursodeoxycholate than with infusion of tauroursodeoxycholate (ZoUBoULIs-VAFIADIS et al, 1982).…”

Section: Discussionmentioning

confidence: 93%

“…As has been shown in the present study as well as in our previous report (KITANI and KANAI, 1982), in the case of ursodeoxycholate infusion, the bile salt excretion rate dropped to one half of its maximal value during the maximal choleretic period. Thus, it seems possible that they actually underestimated the value of maximal bile salt excretion rate in ursodeoxycholate-infused rats (ZOUBOULIS-VAFIADIS et al, 1982).…”

Section: Discussionmentioning

confidence: 99%

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Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

Kitani

Kanai

1985

Jpn.J.Physiol

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The effect of i.v. infused ursodeoxycholate (1.2 ,umol/(min 100 g body weight)) was compared in control rats and in taurine supplemented (i.p. administration of a taurine solution) and taurine deprived (oral administration of 13-alanine) rats. In the control rats, the bile water output during the first hr was significantly lower than that of the second hr, while the bile salt output was significantly lower in the second hr. In j3-alanine pretreated rats, the increase in the bile flow in the first hr was more rapid compared to control rats, and the bile flow rate reached a peak earlier. The first hr and total 2 hr bile water outputs were significantly higher in the j3-alanine pretreated rats compared to the corresponding bile flow values of the control rats, while the bile salt outputs were significantly lower than respective control values. In taurine supplemented rats, the increase in bile flow in the second hr was less than in control rats, while the bile salt excretion rate was the highest among the three rat groups. Thus, among these three groups, the bile flow and bile salt excretion rate during the first hr and 2 hr total infusion periods were negatively correlated. On the other hand, a significant positive correlation was observed between the bile flow rate for 1 or 2 hr and bile salt concentration in the liver examined after a 1 or 2 hr bile salt infusion. These results seem most easily explained by our previous thesis that at least part of the bile is produced not by the excretion of bile salt into the bile canaliculus but by its presence inside the hepatocyte (secretory mechanism).

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Section: Discussionsupporting

confidence: 94%

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 70%

Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

Kitani

Kanai

1985

Jpn.J.Physiol

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23-Methyl-3α, 7β-dihydroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat

et al. 1988

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A side chain derivative of ursodeoxycholic acid, 23-methylursodeoxycholic acid, was synthesized and the effect of i.v. infusion of the acid at different doses (0.75, 1.5, 3.0 and 6.0 mumoles per min per kg body weight over 1 hr) on bile flow, on its hepatic biotransformations and on biliary lipid secretion has been studied in bile fistula rats. The results were compared with those of ursodeoxycholic and cholic acid administered under similar conditions. 23-Methylursodeoxycholic acid is poorly secreted into bile and poorly taurine and glycine conjugated, at all infusion doses. Ursodeoxycholic acid is quantitatively recovered at low doses and recovered less at high infusion rates. Cholic acid is almost entirely recovered at all infusion doses. Ursodeoxycholic acid conjugation pattern is dependent on the dose, and glucuronidation and sulfation operate at high doses. Cholic acid is taurine conjugated at low doses; at high doses, large amounts of unconjugated bile acids are observed. Methylursodeoxycholic acid presents a delayed secretion and hypercholeresis. Ursodeoxycholic acid presents similar results at high infusion rates, possibly by reaching a high intrahepatic concentration of free form. The octanol/water partition coefficients of ursodeoxycholic acid and 23-methylursodeoxycholic acid are similar and higher than that of cholic acid. A chole-hepatic shunting of 23-methylursodeoxycholic acid may explain both the low recovery in bile and hypercholeresis and is consistent with its hydrophilicity of cholic acid, on the contrary, makes possible its high recovery in bile. The effect on biliary lipid secretion is unpredictable and affected by the dose and, in consequence, by the conjugation pattern of the bile acid.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypercholeresis induced by unconjugated bile acid infusion correlates with recovery in bile of unconjugated bile acids

et al. 1991

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Using the isolated perfused rat and hamster liver, the relationship between bile flow, bile acid secretion rate and bile acid biotransformation after the injection of a small, bolus dose of radioactive ursodeoxycholate or of its C23 homolog, norursodeoxycholate, was examined. Ursodeoxycholate was promptly secreted into bile mostly as amino acid conjugates; less than 3% was secreted in unchanged form in the rat and less than 2% in the hamster. In contrast, norursodeoxycholate was secreted slowly, and biotransformed into glucuronide conjugates and unconjugated trihydroxy derivatives; it was also secreted in part in unchanged form. In the rat, 7% was secreted in unconjugated trihydroxy derivatives and 3% in unchanged form; in the hamster, 7% was secreted as unconjugated trihydroxy derivatives and 4% in unchanged form. The secreted bile acid species that showed the highest correlation with bile flow by far was always the unconjugated form in both rat and hamster. By multiple regression analysis, the apparent choleretic activity (microliters of induced bile flow per micromoles recovered bile acid molecules) indicated marked hypercholeresis for the unconjugated bile acid marked hypercholeresis for the unconjugated bile acid with values ranging from 100 to 300 microliters/mumol. Bile flow also correlated with total bile acid recovery for ursodeoxycholate in rat and norursodeoxycholate in hamster, but in all studies the apparent choleretic activity was far lower. Other calculations indicated that most bile flow during the first 30 min was induced by secretion of the unconjugated bile acid species in all experiments, the proportion ranging from 50% to 90%. The results indicate that when a bolus of ursodeoxycholate or norursodeoxycholate is presented to the perfused rodent liver, the secretion of the unchanged bile acid appears to be responsible for most of the bile flow, probably by a cholehepatic shunting mechanism.

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Conjugation is rate limiting in hepatic transport of ursodeoxycholate in the rat

Cited by 19 publications

References 0 publications

Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

Ursodeoxycholate-induced choleresis in taurine-deprived and taurine-supplemented rats.

23-Methyl-3α, 7β-dihydroxy-5β-cholan-24-oic acid: Dose-response study of biliary secretion in rat

Hypercholeresis induced by unconjugated bile acid infusion correlates with recovery in bile of unconjugated bile acids

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